Neuroplasticity: functional MRI techniques M.A. Rocca

Transcription

1 Neuroplasticity: functional MRI techniques M.A. Rocca Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.

2 Outline of the presentation Does fmri disclose sensible changes in MS phenotypes? Which is the role of fmri changes? Are those changes correlated with structural damage? Investigating the resting brain: a valuable approach? Function of the spinal cord GM? Can fmri have a prognostic role? Can fmri be useful to monitor treatment effects?

3 MS phenotypes CIS vs non-disabled RRMS Mildly disabled RRMS SPMS vs vs SPMS mildly disabled RRMS Precuneus, IPL, MFG SII SMC Non-disabled vs mildly disabled RRMS Precuneus, CMA, MFG SMC, SMA MFG, IPL Thalamus Rocca et al., Lancet Neurol 2005

4 Adaptive role BMS L SMC vs T2 lesion volume: r = 0.78, p < t values Rocca et al., Neurology 2010 Pediatric MS t values L SMC vs T2 lesion volume: r = 0.78, p < Rocca et al., Hum Brain Mapp 2009

5 Adaptive role Object manipulation Healthy subjects: object manipulation MS patients: simple motor task Filippi et al., NeuroImage 2004 MNS task MNS task: patients vs controls Simple and MNS tasks interaction: patients vs controls Rocca et al., Neurology 2008

6 Maladaptive role F MS day 1 vs baseline + day 4 SPMS (reduced activations) PPMS STG L SMA R thalamus L putamen MFG L SMC, R MFG, SMA, CMA R cerebellum Insula L SMC, MFG, SMA, CMA Rocca et al., Hum Brain Mapp 2007 Rocca et al., Neurology 2010 Filippi et al., NeuroImage 2002

7 Adaptive-Maladaptive role MS patients vs controls PASAT Controls Alertness task IFG, MFG, IP cortex, STG, MTG, bilaterally; SMA; R anterior cingulate Mildly impaired Severely impaired Incompatibility task Recall Task Working memory task IFG, MFG, STG, MTG, transverse TG, BG, bilaterally; R lateral premotor area; L thalamus Mainero et al., NeuroImage 2004 Penner et al., J Neurol 2003

8 Impaired functional reserve Controls vs CIS (Variable attentional control task) RRMS patients (Go-NoGo task) Load-related abnormalities in the recruitment of putamen in CIS patients Tortorella et al., MSJ 2013 Bonnet et al., Neurology 2010

9 L SMC response fmri vs structural damage SMA, CMA Rocca et al., Ann Neurol 2002 SII CMA Average lesion MD [mm2s-1] L SMC response SMC, SMA, IPS r = 0.88 p < MD of the NABT [mm2s-1] r = 0.81 p < 0.005

10 fmri vs structural damage L R SMC 0.12 Cerebellum Increased connectivity in patients Similar connectivity in patients and controls SMA to L primary SMC: CST LL (r = 0.64, p = 0.04) R SMC to cerebellum: DRT-FA (r = -0.73, p = 0.02) DRT-MD (r = 0.85, p = 0.004) Rocca et al., Neurology Pediatric HV Pediatric RRMS Adult HV Adult CIS Adult RRMS Connectivity coefficients vs CC and CST damage (r = to 0.40) Rocca et al., Radiology 2010 SMC Mean path coefficient SMA 0.14

11 From regions to networks Within-network abnormalities Executive Sensorimotor Inter-network abnormalities Ventral and dorsal attention Sensorimotor I Sensorimotor II Primary visual network p= R frontoparietal L frontoparietal SN p= 0.0 DMN 3 p= p<0.001 Auditory network L WMN R WMN Roosendaal et al., Brain 2010 ECN Rocca et al., Neurology 2012 DMN Secondary visual network

12 From regions to networks MS connectome DMN RS FC in progressive MS HC L R Precun MCC SFG MCC Thal CP HC PPMS SPMS Put MTG Cereb ITG (cr I) Cereb (cr II) Rocca et al., Neurology 2010 ITG CI Cereb (cr I) Cereb (cr II) MCC Caud Thal Thal MTG OFC Sup TP ITG PASAT (r=0.42, p<0.001) CC FA and JD (r from 0.54 to 0.87, p<0.001) Cingulum FA (r=0.83, p<0.001) MTG OFC MCC ACC Correlations between DMN RS FC and: ACC Cereb (cr I) Cereb (cr II) MCC ACC OFC MTG Pall Cereb (cr I) Cereb (VIII) ITG MCC Ling ACC MTG Put MTG Cereb (cr I) OFC ITG Sup ITG Cereb Cereb (cr I) TP Cereb (cr II) (IV-V) Rocca et al., Brain Struct & Funct 2014 ACC

13 From regions to networks Intra/Inter-network abnormalities in pediatric MS Intra-network abnormalities Inter-network abnormalities Sensorimotor II Primary visual network Sensorimotor I p= SN p =0 Auditory network.02 DMN CI explained by: cingulum FA CC MD R precuneus RS FC C-index=0.99 Rocca et al., Neurology 2014 L WMN R WMN ECN Secondary visual network Rocca et al., Human Brain Mapp 2014

14 Task-related average signal change [%] Cervical cord p=0.05 vs controls % 0.7 % 3. 3 % 1.1 % p=0.02 vs controls 3.9 % 1.3 % Cord average signal change (%) Cord fmri in progressive MS Controls SPMS PPMS Progressive MS vs controls: p=0.003 SPMS vs PPMS: p=0.05 Valsasina et al., Hum Brain Mapp Cord fmri vs fatigue Controls RRMS SPMS Valsasina et al., JNNP 2010 Rocca et al., Mult Scler 2012

15 Prognosis One-year follow up Good clinical recovery Unimpaired hand Poor clinical recovery Impaired hand Impaired vs. unimpaired hand Mezzapesa et al., Hum Brain Mapp 2007

16 Longitudinal changes CIS/R DLPFC 1 year activation change Cognitively improved vs stable patients Audoin et al., Mult Scler 2008 Early RRMS /L IPL 1 year activation change L IPL vs worse SDMT performance Loitfelder et al., PlosOne 2014

17 Monitoring treatment Controls Baseline Stroop task and rivastigmine MS patients Parry et al., Brain weeks 3, 4-diaminopyridine vs placebo 1 session Performance improvement vs fmri activity Mainero et al., Neurology 2004 Tomassini et al., Neurorehabil Neural Repair 2012

18 L Stroop facilitation condition: TG vs CG R RSN TG p=0.01 L dorsolateral PFC L TG PCC/Precuneus 0 t values 10 Stroop interference condition: TG vs CG B dorsolateral PFC L R TG CG p=0.02 RS fluctuations L p=0.006 R IPL Filippi et al., Radiology 2011 CG DMN RS fluctuations FU R F values Baseline CG Executive network L PFC RS fluctuations Stroop task vs cognitive rehabilitation RS fluctuations Monitoring treatment PCC Salience network p=0.02 ACC R TG CG

19 Monitoring treatment L DLPFC anodal tdcs stimulation 10 days * * ** 6 months R IPL [DMN] R precuneus [DMN] *Depression ACC [salience] R MFG L DLPFC [executive] **QoL Parisi et al., MSJ 2014 R IPL Mattioli et al., MSJ 2015 Normalized variable importance 6 month follow up

20 Multi-centre studies Motor task Cognitive task Wegener et al., Eur J Neur 2007 Rocca et al., Hum Brain Mapp 2009 Rocca et al., Hum Brain Mapp 2014

21 Conclusions Brain functional reorganization is a common phenomenon in MS patients independent of disease duration and clinical phenotype. Variable patterns of cortical rewiring with the potential to limit the functional consequences of tissue damage occur in MS patients, suggesting that their disability is likely to result from the balance between structural damage and brain reorganization, rather then being a mere reflection of tissue disruption. Together with adaptive plasticity, maladaptive plasticity can occur in brain systems, which contributes to accumulation of disability and cognitive impairment. Improved understanding of recovery mechanisms may guide the development of new recovery-oriented strategies in MS.